The Medicines Company's PCSK9 Inhibitor for Cholesterol Looks Good in Phase III

Cholesterol Formation

The Medicines Company’s inclisiran hit its primary and secondary endpoints in its Phase III trial to decrease LDL-cholesterol through twice-a-year dosing. Inclisiran is a PCSK9 inhibitor, a class of anti-cholesterol medications used to treat patients who don’t respond to statins. The other two PCSK9 drugs on the market are Amgen’s Repatha and Sanofi and Regeneron’s Praluent. Although The Medicines Company didn’t release efficacy data yet, the selling point is apparently the two-times-per-year dosing, although there have been some safety concerns in earlier trials.

In general, Amgen and Sanofi/Regeneron’s products have had difficulties in gaining traction in the marketplace. The issue has mostly been price. Before price cuts over the last two years, both drugs ran about $14,000 for a year’s supply. They have cut prices to as low as $5,850 a year. Payers have been resistant to paying for the drugs, especially since statins typically run about $50 per month. As a result, the drugs have tended to be reserved for patients with extremely high, untreatable cases of cholesterol, often with inherited diseases.

The Medicines Company released results from the ORION-11 trial of inclisiran sodium 300 mg, which was well tolerated and confirmed the safety profile “at least as favorable” as seen in the ORION-1 Phase II and ORION-3 open label extension studies.

ORION-11 was a pivotal Phase III, placebo-controlled, double-blind, randomized trial evaluating the efficacy, safety, and tolerability of inclisiran administered subcutaneously in 1,617 patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and elevated LDL-C despite maximum doses of statin therapy, with or without ezetimibe.

Ezetimibe is sold by Merck under the brand name Zetia. Zetia has a different mode of action than statins. Statins prevent the production of cholesterol by the liver. Ezetimibe lowers blood cholesterol by decreasing the absorption of cholesterol from the intestine.

ORION-11 was conducted at 70 locations in seven countries outside the U.S. The primary endpoints were percentage change in LDL-C from baseline to day 510 and time-adjusted percentage change in LDL-C from baseline after day 90 and up to day 540. Key secondary endpoints were mean absolute change at Day 510, the average absolute reduction from Day 90 up to Day 540, and changes in other lipids and lipoproteins.

“This is a momentous occasion that further reinforces our confidence in the tremendous potential of inclisiran to fundamentally change the treatment of cardiovascular disease,” stated Mark Timney, The Medicines Company’s chief executive officer. “I am proud of our clinical development team’s commitment to expeditiously advance this first-in-class investigational therapy that could help millions of ASCVD patients achieve treatment goals and live longer, healthier lives.”

The company is also expecting data readings for ORION-9 and ORION-10 later in the third quarter in advanced of regulatory submissions to the U.S. Food and Drug Administration (FDA) in the fourth quarter and in Europe in the first quarter of 2020. Patients who have completed their Phase III trials are enrolling in ORION-8, a long-term extension study where they will receive the drug for three years to determine long-term dosing efficacy, safety and tolerability.

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